Diabetes mellitus is one of the most important public health problems affecting millions of people worldwide. An early and accurate diagnosis of diabetes mellitus has critical importance for the medical treatments of patients. In this study, first, artificial neural network (ANN) and classification and regression tree (CART)-based approaches are proposed for the diagnosis of diabetes. Hybrid ANN-GA and CART-GA approaches are then developed using a genetic algorithm (GA) to improve the classification accuracy of these approaches. Finally, the performances of the developed approaches are evaluated with a Pima Indian diabetes data set. Experimental results show that the developed hybrid CART-GA approach outperforms the ANN, CART, and ANN-GA approaches in terms of classification accuracy, and this approach provides an efficient methodology for diagnosis of diabetes mellitus.